Secondhand smoke is a common early-life exposure that may contribute to future risk for obesity. Epidemiologic studies have consistently reported positive associations between prenatal or postnatal exposure to secondhand smoke with childhood obesity. However, very few studies have attempted to disentangle the effects of prenatal and postnatal exposures or have incorporated a tobacco-specific biomarker of exposure. Furthermore, the mechanisms underlying the secondhand smoke-obesity associations are unknown. The goal of this project is to explore the timing and mechanisms of the previously observed associations between exposure to secondhand smoke and obesity, incorporating 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a novel and potentially more accurate indicator of exposure. Understanding when and how exposure to secondhand smoke impacts obesity risk may inform new public health strategies with potential relevance for both smoking cessation and obesity prevention. During the training phase of this award, Dr. Moore will use didactic instruction, individually mentored training, and independent study to develop expertise in three content areas: 1) secondhand smoke exposure assessment; 2) nutritional epidemiology; and 3) advanced statistical methods. This training will be applied to a research project that will leverage the resources and infrastructure of an ongoing, longitudinal cohort of 1,410 mother-child pairs (Healthy Start, R01DK076648, PI: Dabelea), which was recently included in the Environmental Influences on Child Health Outcomes (ECHO) consortium (1UG3OD023248-01; PI: Dabelea). She will examine the association of prenatal and postnatal exposures to secondhand smoke with repeated measures of adiposity from birth to 5 years (Aim 1). During the independent phase of this award, Dr. Moore will validate the data yielded from Aim 1 by using NNAL to characterize exposure to secondhand smoke. She will then explore the extent to which the secondhand smoke-obesity associations are mediated by oxidative stress and inflammation or modified by early-life nutrition and socioeconomic status (Aim 3). Dr. Moore is well-equipped to perform this research based on: 1) her research background and interests investigating the impact of exposures to environmental chemicals on childhood obesity; 2) her access to the unique, well-characterized Healthy Start cohort, which will allow for an in-depth exploration of the timing and mechanisms of the secondhand smoke-obesity associations; and 3) her access to the extensive resources provided by her mentorship team and institution. The proposed research and training plan will prepare her for an independent career examining the impact of environmental exposures on childhood metabolic disorders.